A Novel Exploration of the Choroidal Vortex Vein System: Incidence and Characteristics of Posterior Vortex Veins in Healthy Eyes.

Purpose: The purpose of this study was to investigate the incidence and characteristics of posterior vortex veins (PVVs) in healthy eyes and explore their relationship with age and refractive status. Methods: This retrospective cross-sectional analysis encompassed 510 eyes from 255 consecutive healthy participants. Wide-field optical coherence tomography angiography (WF-OCTA) imaging was used to assess the presence of PVVs. Eyes were classified according to refractive status (emmetropia, low and moderate myopia, and high myopia) and age (minors and adults). The incidence and characteristics of eyes with PVVs were analyzed. Results: Participants (mean age = 30.60 ± 21.12 years, 47.4% men) showed a mean refractive error of -2.83 ± 3.10 diopters (D; range = -12.00 to +0.75). PVVs were observed in 16.1% (82/510) of eyes. Of these, 39% (32/82) had PVVs in one eye and 61% (50/82) in both eyes. The mean number of PVVs per eye was 1.65 ± 1.05 (range = 1-6). PVVs are mainly around the optic disc (78%, 64/82) of eyes with PVVs and less in the macular area (6.1%, 5/82) or elsewhere (15.9%, 13/82). PVV incidence correlated with refractive status: 10.3% (22/213) in emmetropia, 16.6% (31/187) in low and moderate myopia, and 26.4% (29/110) in high myopia (P = 0.001), but not with age. Refractive status was the key predictor of PVV occurrence (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.02-2.06, P = 0.038). Conclusions: This study confirms PVVs' presence in healthy eyes, highlighting their inherent existence and susceptibility to alterations due to refractive conditions. These findings enhance our understanding of the vortex vein system and its distribution within the eyes.

Nerve growth factor (Ngf) gene-driven semaphorin 3a (Sema3a) expression exacerbates thoracic aortic aneurysm dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease and currently there is no pharmacological therapy. Sympathetic nerve overactivity plays an important role in the development of TAAD. Sympathetic innervation is mainly controlled by nerve growth factor (NGF, a key neural chemoattractant) and semaphoring 3A (Sema3A, a key neural chemorepellent), while the roles of these two factors in aortic sympathetic innervation and especially TAAD are unknown. We hypothesized that genetically manipulating the NGF/Sema3A ratio by the Ngf -driven Sema3a expression approach may reduce aortic sympathetic nerve innervation and mitigate TAAD progression. A mouse strain of Ngf gene-driven Sema3a expression (namely NgfSema3a/Sema3a mouse) was established by inserting the 2A-Sema3A expression frame to the Ngf terminating codon using CRISPR/Cas9 technology. TAAD was induced by ß-aminopropionitrile monofumarate (BAPN) both in NgfSema3a/Sema3a mice and wild type (WT) littermates. Contrary to our expectation, the BAPN-induced TAAD was severer in NgfSema3a/Sema3a mice than in wild-type (WT) mice. In addition, NgfSema3a/Sema3a mice showed higher aortic sympathetic innervation, inflammation and extracellular matrix degradation than the WT mice after BAPN treatment. The aortic vascular smooth muscle cells isolated from NgfSema3a/Sema3a mice and pretreated with BAPN in vivo for two weeks showed stronger capabilities of proliferation and migration than that from the WT mice. We conclude that the strategy of Ngf -driven Sema3a expression cannot suppress but worsens the BAPN-induced TAAD. By investigating the aortic phenotype of NgfSema3a/Sema3a mouse strain, we unexpectedly find a path to exacerbate BAPN-induced TAAD which might be useful in future TAAD studies.

Persistent Placoid Maculopathy: Lichen-like Lesions Growing between Retinal Pigment Epithelium and Bruch's Membrane.

PURPOSE: To report the novel imaging findings in persistent placoid maculopathy (PPM) from the first case series of Asian subjects. DESIGN: Retrospective observational case series. SUBJECTS: Patients with PPM from 2013 to 2023. METHODS: Medical records and multimodal images from each visit were analyzed. MAIN OUTCOME MEASURES: Imaging and follow-up findings. RESULTS: Twenty-one eyes of 16 patients were included. Mean age was 61 (range, 48-84) years old. Five patients showed bilateral involvement. Persistent placoid maculopathy lesions were unremarkable on color fundus photography, autofluorescence, and fluorescein angiography. Hypofluorescent spots with a lichen-like appearance presented in all phases of indocyanine green angiography, which were most prominent in the late phase and presented in a fused (71%) or clustered (29%) pattern. The hypofluorescence correlated with the lesions between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) with moderate reflectivity on OCT, and the thickness ranged from slit-like to mound-like. The intensity of hypofluorescence sometimes varied in the same eye and correlated with the thickness of sub-RPE lesions on OCT. No abnormal blood flow signals were detected in either the sub-RPE space or choriocapillaris slab of OCT angiography across the PPM lesions. Peripapillary (5 eyes, 24%) and extra posterior pole (2 eyes, 10%) involvements were seen, the former sparing the ß zones of optic discs. Ten eyes of 7 patients were followed up (median, 26 months; range, 2-121 months). During follow-up, the lichen-like lesions spread and migrated slowly without changing the plane patterns of the first visit and were limited to sub-RPE growth. The fused lichen-like pattern sprawled around the enlarged base. The clustered lichen-like pattern gradually loosened. Ten eyes (48%, 9 eyes in the fused pattern, 1 eye in the clustered pattern) had secondary choroidal neovascularization (CNV) at the first visit, with type I (6 eyes, 5 of which were polypoidal choroidal vasculopathy) and type II (4 eyes). No new CNV developed during follow-up. CONCLUSION: Persistent placoid maculopathy lesions were located in the sub-RPE space, as determined by multimodal imaging. Spreading and migration between the RPE and BM may account for their unique lichen-like appearance and progression pattern. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A prospective observation of influence of anti-VEGF on optic disc vasculature in nAMD patients.

BACKGROUND: This study aims to investigate the short-term changes in relatively normal retinal vessels following anti-vascular endothelial growth factor (anti-VEGF) therapy in nAMD patients, an area that currently represents a research gap. METHODS: In this prospective study, we enrolled patients newly diagnosed with neovascular age-related macular degeneration (nAMD) and received standardized monthly anti-VEGF therapy for three months. Follow-ups were conducted at baseline and 1-week, 1-month, 2-months and 3-months post first injection. Assessment indicators included radial peripapillary capillary vascular density (RPC-VD) and retinal nerve fiber layer (RNFL) thickness in different optic disk regions using optical coherence tomography angiography, as well as intraocular pressure (IOP). RESULTS: 68 nAMD patients (68 eyes) were included in this study. Significant reductions of RPC-VD and increases of RNFL thickness primarily in the nasal regions were observed 1-week post anti-VEGF (adjusted P < 0.05). Significant negative correlations were found between 1-week changes in RPC-VD and RNFL thickness in the nasal sectors (P < 0.05). From 1 to 3 months post-injection, RPC-VD and RNFL thickness essentially returned to baseline levels. Throughout the follow-up periods, IOP remained stable (P > 0.05). CONCLUSION: Anti-VEGF treatments transiently influence the relatively normal retinal vessels, which might lead to nerve fiber edema, predominantly on the nasal side of the optic disk.

Quantitative evaluation of choroidal and retinal microvasculature post-alcohol consumption: A pilot study.

PURPOSE: The aim of this study was to assess the impact of acute, heavy alcohol consumption on the ocular microvasculature, providing insight into the largely unexplored response of microvascular structures to excessive drinking. METHODS: Healthy volunteers in this prospective pilot study were tasked with consuming spirits, wine, and water at different times. Alcohol intake was measured according to body weight (g/kg). The ocular microvascular parameters primarily including choroidal volume (CV) and choroidal vessel volume (CVV) reflecting arteriolovenularity, and choroidal capillary density (CCD) reflecting capillary, were evaluated using swept-source optical coherence tomography angiography at baseline and 0.5-, 1-, 2-, and 3-hour post-consumption. RESULTS: A total of 34 eyes underwent 170 successful examinations in this study. After consuming spirits or wine, we observed significant decreases in CV and CVV values (all P < 0.01 for 0.5-, 1-, 2-, and 3-hour post-consumption), along with significant increase in CCD (P < 0.05 at 0.5-, 1-, 2-hour post-spirits consumption and 1-hour post-wine consumption). The most pronounced changes occurred 1-hour after spirits or wine consumption (all P < 0.001 in both univariate and multivariate model). However, post-consumption changes in the ocular microvasculature showed no significant differences between spirits and wine (P > 0.05). Additionally, no significant differences were observed in any parameters after water intake (all P > 0.05). CONCLUSIONS: Excessive alcohol consumption leads to ocular arteriolovenular vasoconstriction and capillary vasodilation, most evident 1-hour post-consumption of spirits and wine. Our research provides insight into alcohol's immediate ocular microvascular effects, hinting at systemic microvascular effects.

Exploring Cutting-Edge Approaches to Potentiate Mesenchymal Stem Cell and Exosome Therapy for Myocardial Infarction.

Cardiovascular diseases (CVDs) continue to be a significant global health concern. Many studies have reported promising outcomes from using MSCs and their secreted exosomes in managing various cardiovascular-related diseases like myocardial infarction (MI). MSCs and exosomes have demonstrated considerable potential in promoting regeneration and neovascularization, as well as exerting beneficial effects against apoptosis, remodeling, and inflammation in cases of myocardial infarction. Nonetheless, ensuring the durability and effectiveness of MSCs and exosomes following in vivo transplantation remains a significant concern. Recently, novel methods have emerged to improve their effectiveness and robustness, such as employing preconditioning statuses, modifying MSC and their exosomes, targeted drug delivery with exosomes, biomaterials, and combination therapy. Herein, we summarize the novel approaches that intensify the therapeutic application of MSC and their derived exosomes in treating MI.

Choroidal Vein Alterations in Pachychoroid Disease With Choroidal Vascular Hyperpermeability: Evaluated by Wide-Field Indocyanine Green Angiography.

Purpose: The purpose of this study was to investigate choroidal vein (ChV) morphological features in pachychoroid disease (PCD) with choroidal vascular hyperpermeability (CVH). Methods: This retrospective study assessed subfoveal choroidal thickness (SFCT) and CVH area numbers and locations of recruited patients with PCD using multimodal images. ChV alteration patterns, including fusiform, bulbosity, sausaging, confluence, and anastomoses, as well as asymmetric ChVs, dominant ChVs, and non-dominant ChVs, were evaluated using wide-field indocyanine green angiograms. Results: Of 68 PCD eyes from 35 patients (mean age: 46.16 ± 6.28 years, 71.4% men), 2.9% had uncomplicated pachychoroid, 32.4% had pachychoroid pigment epitheliopathy (PPE), 55.9% central serous chorioretinopathy (CSC), and 8.8% pachychoroid neovasculopathy (PNV). Mean SFCT was 468.65 ± 131.40 µm. Among 419 CVH areas, ChV fusiform, ChV bulbosity, and ChV sausaging accounted for 35.8%, 35.1%, and 29.1%, respectively; 21.2% had ChV confluence and 11.9% had ChV anastomoses. At CVH areas, 13.1% had retinal pigment epithelium (RPE) leakage. ChV fusiform is steadily declining (37.4%, 36.8%, and 22.9%, respectively), and ChV sausaging, ChV anastomoses, and ChV confluence are increased gradually in the PPE, CSC, and PNV groups (21.4%, 30.0%, and 37.1%; 11.4%, 11.1%, and 20.0%; and 19.8%, 20.9%, and 28.6%, respectively). Dominant ChVs had higher CVH area numbers than non-dominant ChVs in the PPE and CSC groups (P = 0.010, P = 0.001). Conclusions: Different patterns of ChV alterations, including the newly identified ChV confluence, are commonly present at CVH areas in PCD. The CVH areas in PCD eyes are primarily located within the dominant ChVs. These findings provide crucial evidence for advancing our understanding of the underlying mechanisms of PCD pathogenesis.

Acacetin Alleviates Cardiac Fibrosis via TGF-ß1/Smad and AKT/mTOR Signal Pathways in Spontaneous Hypertensive Rats.

INTRODUCTION: Attenuating cardiac fibroblasts activation contributes to reducing excessive extracellular matrix deposition and cardiac structural remodeling in hypertensive hearts. Acacetin plays a protective role in doxorubicin-induced cardiomyopathy and ischemia/reperfusion injury. The aim of this study was to investigate the potential molecular mechanisms underlying the protective role of acacetin on hypertension-induced cardiac fibrosis. METHODS: Echocardiography, histopathological methods, and Western blotting techniques were used to evaluate the anti-fibrosis effects in spontaneous hypertensive rat (SHR) which were daily intragastrically administrated with acacetin (10 mg/kg and 20 mg/kg) for 6 weeks. Angiotensin II (Ang II) was used to induce cellular fibrosis in human cardiac fibroblasts (HCFs) in the absence and presence of acacetin treatment for 48 h. RESULTS: Acacetin significantly alleviated hypertension-induced increase in left ventricular (LV) posterior wall thickness and LV mass index in SHR. The expressions of collagen-1, collagen-III, and alpha-smooth muscle actin (α-SMA) were remarkedly decreased after treatment with acacetin (n = 6, p < 0.05). In cultured HCFs, acacetin significantly attenuated Ang II-induced migration and proliferation (n = 6, p < 0.05). Moreover, acacetin substantially inhibited Ang II-induced upregulation of collagen-1 and collagen-III (n = 6, p < 0.05) and downregulated the expression of alpha-SMA in HCFs. Additionally, acacetin decreased the expression of TGF-ß1, p-Smad3/Smad3, and p-AKT and p-mTOR but increased the expression of Smad7 (n = 6, p < 0.05). Further studies found that acacetin inhibited TGF-ß1 agonist SRI and AKT agonist SC79 caused fibrotic effect. CONCLUSION: Acacetin inhibits the hypertension-associated cardiac fibrotic processes through regulating TGF-ß/Smad3, AKT/mTOR signal transduction pathways.

Hyperfluorescence of choroidal arteries in the peripheral fundus on late-phase ICGA.

AIMS: To correlate the hyperfluorescent lines in the peripheral fundus on late-phase indocyanine green angiography (ICGA) to infrared and optical coherence tomography (OCT) findings. METHODS: This is a retrospective, cross-sectional study. Multimodal imaging data, including ICGA, fluorescein angiography, infrared imaging, and OCT were analyzed. The hyperfluorescent lines were categorized into 2 grades according to their extents. In addition, serum levels of apolipoprotein (Apo) A and B were measured by enzyme linked immunosorbent assay. RESULTS: A total of 247 patients who underwent multimodal imaging were reviewed. The hyperfluorescent lines in the peripheral fundus on late-phase ICGA were detected in 96 patients, and were correlated to superficial choroidal arteries by infrared imaging and OCT. The incidence of hyperfluorescent choroidal arteries in the peripheral fundus (HCAP) on late-phase ICGA increased in groups of older ages (0-20 years, 4.3%; 20-40 years, 2.6%; 40-60 years, 48.9%; >60 years, 88.7%; p < 0.001). In addition, the mean age increased with the grades of HCAP (grade 1, 52.3 ± 10.8 years; grade 2, 63.3 ± 10.5 years; p < 0.001). The hyperfluorescence was also detected in posterior choroidal arteries in 11 eyes, all patients in grade 2. There was no significant correlation between grades of HCAP and gender, or serum level of ApoA and ApoB. CONCLUSION: The occurrence and grades of HCAP increased with age. The superficial location of choroidal arteries in the peripheral fundus exposes their hyperfluorescence on late-phase ICGA. HCAP might reveal the local lipid degeneration of choroidal artery walls, according to ICG binding properties.

Conversion of primary liver cancer after targeted therapy for liver cancer combined with AFP-targeted CAR T-cell therapy: a case report.

Primary liver cancer (PLC) that originates in the liver is a malignant tumor with the worst prognosis. Hepatocellular carcinoma (HCC) is the most common type of PLC. Most PLC cases are diagnosed at advanced stages mainly due to their insidious onset and rapid progression. Patients with PLC undergo surgical intervention or localized treatment, but their survival is often affected by its high relapse rate. Medical treatment is the primary option for patients with liver cancer, especially with advanced extrahepatic metastases. Molecular targeted therapy exerts an anti-tumor effect by acting on various signaling pathways involved in molecular pathogenesis; however, high drug resistance and low therapeutic responsiveness of PLC to molecular targets challenge the treatment option. In recent years, after surgical intervention, radiotherapy, chemotherapy, and/or molecular targeted therapy, autologous cell immunotherapy has been adopted for PLC. As a typical autologous cell immunotherapy, CAR T-cell therapy uses genetically modified T cells to express tumor-specific chimeric antigen receptors (CARs). Its targeting ability, persistent nature, and tumor-killing function result in a significant impact on the treatment of hematological tumors. However, no breakthrough has happened in the research specific to the curation of lung cancer, liver cancer, breast cancer, and other common solid tumors. In this context, a combination of molecular targeted therapy and CAR T-cell therapy was used to treat a patient with advanced HCC to achieve a partial remission(PR) and facilitate further liver transplantation.

Convolutional neural network for detecting rib fractures on chest radiographs: a feasibility study.

BACKGROUND: Chest radiography is the standard investigation for identifying rib fractures. The application of artificial intelligence (AI) for detecting rib fractures on chest radiographs is limited by image quality control and multilesion screening. To our knowledge, few studies have developed and verified the performance of an AI model for detecting rib fractures by using multi-center radiographs. And existing studies using chest radiographs for multiple rib fracture detection have used more complex and slower detection algorithms, so we aimed to create a multiple rib fracture detection model by using a convolutional neural network (CNN), based on multi-center and quality-normalised chest radiographs. METHODS: A total of 1080 radiographs with rib fractures were obtained and randomly divided into the training set (918 radiographs, 85%) and the testing set (162 radiographs, 15%). An object detection CNN, You Only Look Once v3 (YOLOv3), was adopted to build the detection model. Receiver operating characteristic (ROC) and free-response ROC (FROC) were used to evaluate the model's performance. A joint testing group of 162 radiographs with rib fractures and 233 radiographs without rib fractures was used as the internal testing set. Furthermore, an additional 201 radiographs, 121 with rib fractures and 80 without rib fractures, were independently validated to compare the CNN model performance with the diagnostic efficiency of radiologists. RESULTS: The sensitivity of the model in the training and testing sets was 92.0% and 91.1%, respectively, and the precision was 68.0% and 81.6%, respectively. FROC in the testing set showed that the sensitivity for whole-lesion detection reached 91.3% when the false-positive of each case was 0.56. In the joint testing group, the case-level accuracy, sensitivity, specificity, and area under the curve were 85.1%, 93.2%, 79.4%, and 0.92, respectively. At the fracture level and the case level in the independent validation set, the accuracy and sensitivity of the CNN model were always higher or close to radiologists' readings. CONCLUSIONS: The CNN model, based on YOLOv3, was sensitive for detecting rib fractures on chest radiographs and showed great potential in the preliminary screening of rib fractures, which indicated that CNN can help reduce missed diagnoses and relieve radiologists' workload. In this study, we developed and verified the performance of a novel CNN model for rib fracture detection by using radiography.

Circ_0061140 Contributes to Ovarian Cancer Progression by Targeting miR-761/LETM1 Signaling.

Previous studies have suggested that circular RNAs (circRNAs) play important regulatory roles in cancer progression. Previous evidence exhibited the aberrant upregulation of circ_0061140 in ovarian cancer. However, the detailed role of circ_0061140 in ovarian cancer progression and its associated mechanism remain largely unknown and need further exploration. The expression of circ_0061140, microRNA-761 (miR-761) and leucine zipper and EF-hand containing transmembrane protein 1 (LETM1) was checked by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blot. Cell Counting Kit-8 (CCK8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, transwell, and tube formation assays were conducted to assess cell functions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the interaction between miR-761 and circ_0061140 or LETM1. Xenograft tumor model was established to analyze the role of circ_0061140 in tumor growth in vivo. Circ_0061140 expression was notably up-regulated in ovarian cancer tissues and cell lines. Circ_0061140 knockdown suppressed the proliferation, migration, invasion, and angiogenesis and triggered the apoptosis of ovarian cancer cells. Circ_0061140 directly interacted with miR-761, and circ_0061140 silencing-mediated anti-tumor effects were partly abolished by miR-761 knockdown in ovarian cancer cells. LETM1 was a direct target of miR-761, and LETM1 overexpression partly counteracted miR-761-induced anti-tumor effects. Circ_0061140 could up-regulate LETM1 expression by sponging miR-761. Circ_0061140 knockdown significantly suppressed xenograft tumor growth in vivo. Circ_0061140 aggravated ovarian cancer progression through miR-761-dependent regulation of LETM1.

Restoration of Mitochondrial Function Is Essential in the Endothelium-Dependent Vasodilation Induced by Acacetin in Hypertensive Rats.

Mitochondrial dysfunction in the endothelium contributes to the progression of hypertension and plays an obligatory role in modulating vascular tone. Acacetin is a natural flavonoid compound that has been shown to possess multiple beneficial effects, including vasodilatation. However, whether acacetin could improve endothelial function in hypertension by protecting against mitochondria-dependent apoptosis remains to be determined. The mean arterial pressure (MAP) in Wistar Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) administered with acacetin intraperitoneally for 2 h or intragastrically for six weeks were examined. The endothelial injury was evaluated by immunofluorescent staining and a transmission electron microscope (TEM). Vascular tension measurement was performed to assess the protective effect of acacetin on mesenteric arteries. Endothelial injury in the pathogenesis of SHR was modeled in HUVECs treated with Angiotensin II (Ang II). Mitochondria-dependent apoptosis, the opening of Mitochondrial Permeability Transition Pore (mPTP) and mitochondrial dynamics proteins were determined by fluorescence activated cell sorting (FACS), immunofluorescence staining and western blot. Acacetin administered intraperitoneally greatly reduced MAP in SHR by mediating a more pronounced endothelium-dependent dilatation in mesenteric arteries, and the vascular dilatation was reduced remarkably by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. While acacetin administered intragastrically for six weeks had no apparent effect on MAP, it improved the endothelium-dependent dilatation in SHR by activating the AKT/eNOS pathway and protecting against the abnormalities of endothelium and mitochondria. Furthermore, acacetin remarkably inhibited Ang II induced apoptosis by inhibiting the increased expression of Cyclophilin D (CypD), promoted the opening of mPTP, ROS generation, ATP loss and disturbance of dynamin-related protein 1 (DRP1)/optic atrophy1 (OPA1) dynamics in HUVECs. This study suggests that acacetin protected against endothelial dysfunction in hypertension by activating the AKT/eNOS pathway and modulating mitochondrial function by targeting mPTP and DRP1/OPA1-dependent dynamics.

AGE-RELATED RETENTIONAL AVASCULAR PIGMENT EPITHELIAL DETACHMENT VIEWED WITH INDOCYANINE GREEN ANGIOGRAPHY.

PURPOSE: Age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) might represent hydrophobic neutral lipid deposits in the Bruch membrane. This study aimed to report retentional avascular pigment epithelial detachment (PED) associated with ASHS-LIA. METHODS: Patients aged ≥50 years who presented a single avascular serous PED without soft drusen or any other retinal or choroidal diseases were retrospectively included. Pigment epithelial detachment was classified as retentional, effusional, or mixed PED based on indocyanine green angiography. Multimodal images were qualitatively and quantitatively evaluated. RESULTS: This study included 74 eyes of 57 patients. Retentional PED, effusional PED, and mixed PED accounted for 91.9%, 4.1%, and 4.1%, respectively. All PEDs were located in the macular region. Seventeen (29.8%) included patients had bilateral PEDs and all were retentional PEDs with a high level of bilateral consistency in the characteristics of PED and ASHS-LIA. All retentional PEDs were within the bounds of ASHS-LIA. The area of retentional PED increased with the ASHS-LIA grade ( P = 0.030). CONCLUSION: Most age-related avascular serous PEDs are retentional PEDs. The location and area of retentional PEDs are consistent with the distribution of ASHS-LIA. These findings suggest that the hydrophobic neutral lipid deposits in the Bruch membrane might be involved in the pathogenesis and be a therapeutic target in age-related retentional avascular PED.

SIRT1 exerts anti-hypertensive effect via FOXO1 activation in the rostral ventrolateral medulla.

The rostral ventrolateral medulla (RVLM) is a pivotal region in the central regulation of blood pressure (BP). It has been documented that silent information regulator 2 homolog 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent multifunctional transcription regulatory factor, has many cardiovascular protective effects. However, the role and significance of SIRT1 in the central regulation of cardiovascular activity, especially in RVLM, remains unknown. Therefore, the aim of this study was to explore the role and underlying mechanism of SIRT1 in the central regulation of cardiovascular activity in hypertension. Spontaneously hypertensive rats (SHRs) were given resveratrol (RSV) via intracerebroventricular (ICV) infusion or injected with SIRT1-overexpressing lentiviral vectors into the RVLM. In vitro experiments, angiotensin II (Ang II)-induced rat pheochromocytoma cell line (PC12 cells) were transfected with forkhead box protein O1 (FOXO1) small interfering RNA (siRNA) before treatment with RSV. Our results showed that SIRT1 activation with RSV or overexpression in the RVLM significantly decreased BP and sympathetic outflow of SHRs. Furthermore, SIRT1 overexpression in the RVLM significantly decreased reactive oxygen species (ROS) production and facilitated the forkhead box protein O1 (FOXO1) activation, accompanied by upregulation of the ROS-detoxifying enzyme superoxide dismutases 1 (SOD1) in the RVLM of SHRs. In PC12 cells, it was found that Ang II could induce oxidative stress and downregulate the SIRT1-FOXO1-SOD1 signaling pathway, which indicated that the suppressed expression of SIRT1 in the RVLM of SHRs might relate to the elevated central Ang II level. Furthermore, the enhanced oxidative stress and decreased SIRT1-FOXO1-SOD1 axis induced by Ang II were restored by treatment with RSV. However, these favorable effects mediated by SIRT1 activation were blocked by FOXO1 knockdown. Based on these findings, we concluded that SIRT1 activation or overexpression in the RVLM exerts anti-hypertensive effect through reducing oxidative stress via SIRT1-FOXO1-SOD1 signaling pathway, which providing a new target for the prevention and intervention of hypertension.

Ageing fundus degenerations of Macaca fascicularis on multi-modal imaging and histopathology: Similarities and differences compared to human.

To characterize the ageing fundus degenerations in Macaca fascicularis, we used multimodal imaging including color fundus photograph, spectral domain optical coherence tomography, fundus autofluorescence, fundus fluorescence angiography, and indocyanine green angiography (ICGA) to survey and track fundus changes of 84 Macaca fascicularis, ranging from 5 to 24 years old over 2 years, and followed by hematoxylin-eosin (HE) and immunofluorescence (IF) staining. The Macaca fascicularis in our cohort showed ageing characteristics different from human, including the more common yellow dot maculopathy, the unique appearance of patchy hyperautoflurescence, and the absence of subretinal drusenoid deposit, basal laminar deposit, geographic atrophy or choroidal neovascularization. Same with human, hard drusen, soft drusen, atherosclerosis, tessellated retina, staining of vessels in peripheral choroid on late-phase ICGA, and peripheral hard drusen were detected. HE and IF staining suggested the patchy hyperautoflurescence to be drusenoid deposits. BMI were significantly higher in the Macaca fascicularis with yellow dot maculopathy and hard drusen, compared to the ones without (p < 0.05). Our study reveals fundus degenerations that develop with ageing in the nonhuman primate of Macaca fascicularis. Their differences and similarities compared to human worth notice by future translational research in degenerative fundus diseases, especially age-related macular degeneration.

Investigation of Serum and Macular Carotenoids in Central Serous Chorioretinopathy.

Purpose: This study aimed to evaluate serum lutein and zeaxanthin levels and macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC). Methods: Fifty-four patients with acute CSC (28-56 years old; 44 men and 10 women) and 62 matched controls were enrolled. Serum lutein and zeaxanthin were measured using the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. MPOD was measured at 7° of eccentricity and reported in parameters as "max" and "mean" optical density (OD) (Visucam 200; Carl Zeiss Meditec). MPOD was re-measured in 9 patients whose subretinal fluid was absorbed. Results: The average max OD and the mean OD in CSC were 0.275 ± 0.047 d.u. and 0.098 ± 0.018 d.u., respectively, which were significantly lower than the control (p < 0.001). The average MPOD value in the unaffected eyes of patients with CSC was 0.298 ± 0.045 for max OD, 0.106 ± 0.017 for mean OD, and both were significantly lower compared with the affected eyes (p < 0.001 for max OD, p = 0.01 for mean OD). In the 9 follow-up patients, the decrease in MPOD was partially recovered. The mean serum level was 409.80 ± 182.52 ng/ml for lutein and 22.97 ± 12.23 ng/ml for zeaxanthin in patients with CSC. In controls, the mean serum level was 393.38 ± 202.44 ng/ml for lutein and 22.16 ± 10.12 ng/ml for zeaxanthin. The difference was not statistically significant (p = 0.649, p = 0.698, respectively). Conclusion: MPOD decreased within 7° of eccentricity in CSC without serum lutein and zeaxanthin changes. The decrease may be due to the subretinal fluid. Whether local oxidative stress is involved in CSC and the supplementation with lutein and zeaxanthin is helpful for CSC requires further investigation.

Characterization of Macrophage-Like Cells in Retinal Vein Occlusion Using En Face Optical Coherence Tomography.

Purpose: To investigate the clinical features of a macrophage-like cell (MLC) obtained by en face optical coherence tomography (OCT) in retinal vein occlusion (RVO). Methods: The study involved 36 patients with treatment-naïve unilateral acute RVO, including 21 branch RVO (BRVO) and 15 central RVO. Vessel density and macular thickness were quantified using OCT angiography. A 3-µm en face OCT slab on the inner limiting membrane in the optic nerve head (ONH) region or macular region was used to visualize the MLCs. The MLCs were binarized and quantified using a semiautomated method. The unaffected fellow eyes served as the control group. Results: The morphology of MLCs appeared larger and plumper in RVO eyes. The mean MLC density in the ONH and macular regions was 2.46 times and 2.86 times higher than their fellow eyes, respectively (p < 0.001). The macular MLC density of the occlusive region was significantly lower than that of the unaffected region in BRVO (p = 0.01). The ONH and macular MLC densities in the non-perfused region were significantly lower than those in the perfused region in all RVO eyes (p < 0.001). The ONH MLC density in RVO eyes was negatively correlated with radial peripapillary capillary vessel density (r = -0.413, p = 0.012). Both ONH and macular MLC densities were positively correlated with macular thickness (r = 0.505, p = 0.002; r = 0.385, p = 0.02, respectively). Conclusion: The increased density and changes of morphology characterized by OCT may indicate generalized activation and aggregation of MLCs in RVO. More MLCs are recruited in the perfused region rather than the non-perfused region. RVO eyes with a higher density of MLCs tend to suffer from the thicker macula.

Investigation on Residual Strength and Failure Mechanism of the Ceramic/UHMWPE Armors after Ballistic Tests.

In this paper, the ballistic damage mechanism and residual bearing capacity of ceramic/backing plate armor were investigated. First, a series of lightweight armors were prepared, consisting of ceramic and ultra-high molecular weight polyethylene fiber-reinforced resin matrix composite (UHMWPE) plates, and were wrapped in a high-strength fabric. Then, the ceramic/UHMWPE armors were hit by one or two bullets, and finally subjected to compression testing. The results showed that the main failure mode of integral ceramic/UHMWPE armors was ceramic brittle fracture. Many zigzag patterns on the compression curve indicated that the specimens had undergone the stages of crack propagation, ceramic fragment reorganization, plastic deformation of UHMWPE backing plate, interlaminar tearing, and overall fracture. The failure of spliced ceramic/UHMWPE armors was mainly due to the dislocation between ceramic sheets; the smooth compression curves indicated that there was no recombination of ceramic fragments and obvious interlayer debonding during the compression. Under the maximum load, each ceramic/UHMWPE armor with ballistic damage did not suddenly break and fail. The structure and thickness of ceramic plates all had an impact on residual strength: under the same structure, the greater the thickness, the greater the residual strength, but the relationship between them was not linear; under the same thickness, the residual strength of the spliced ceramic/UHMWPE armor was higher. The residual strength was also related to the number of shots: after two bullets hit, its value was only one-third of that after one bullet hit.